Stages of Marek's disease virus latency defined by variable sensitivity to interferon modulation of viral antigen expression.

Cytokines in conditioned medium can suppress expression of viral internal antigens (VIA) in lymphocytes latently infected with Marek's disease virus. In the present study, conditioned media produced by spleen cells stimulated with concanavalin A or by mixed-lymphocyte reaction had significantly greater (P < 0.05) VIA-suppressive activity with lymphocytes harvested from birds at 14 days post infection than with those collected at 7 days. This finding defines two stages during the latent period in which sensitivity of lymphocytes to cytokine modulation of viral expression differs. Suppression involved proteins representing immediate-early, early and late viral antigens. Physico-chemical characterization of the suppressive factor in conditioned medium was consistent with that expected of interferon. Indeed, natural interferon prepared from avian reovirus-exposed chicken embryo cells, and recombinant chicken interferon, both mimicked the activity of conditioned medium and were more suppressive with lymphocytes from the later stage of latency.

Interferon modulation of Marek's disease virus genome expression in chicken cell lines.

Lines of chicken lymphoblastoid cells were established from local lesions induced by simultaneous injection of Marek's disease virus and various stimulants of T-cell activation. Lines developed with regular medium had relatively high mean rates of spontaneous expression of viral internal antigen (6.2%). In contrast, lines developed and maintained with conditioned medium generated by mixed-lymphocyte reaction had a 62-fold reduction in the mean rate of viral internal antigen expression (0.1%). The expression rate could be modulated by the removal or re-addition of conditioned medium to the growth medium. Down regulation involved proteins classified as immediate-early (a 14-kDa polypeptide), early (a 38-kDa phosphoprotein), and late (glycoprotein B homologue) antigens, indicating that the block is very early in virus replication. Once initiated in a given cell, replication apparently proceeded unimpeded. Interferon was determined to be largely responsible for the suppressive activity of the conditioned medium, although involvement of other cytokines could not be ruled out. Also, chicken interferon from other sources, including recombinant interferon, was able to similarly suppress viral antigen expression.